In Oklahoma, U.S. Highway 77 runs north–south, paralleling Interstate 35, connecting Texas to Kansas and running for 267.21 miles (430.03 km) through the central part of the state. It passes through many major cities, including Ardmore, Oklahoma City and its suburbs, Guthrie, and Ponca City. It has four lettered spur routes.

US-77 was the first highway in Oklahoma to be paved entirely across the state from border to border. It has been a paved roadway since 1930.

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US-77 enters the state along with I-35 but splits off at the first exit in Oklahoma. Four miles later, it passes through Thackerville. It junctions with State Highway 32 on the west side of Marietta.

North of Marietta, US-77 passes to the west of Lake Murray and its state park. It then enters Carter County and Ardmore, where it is named Commerce Street through the city limits over a four-lane divided thoroughfare that includes frontage roads on each side from just south of SH-199 (West Broadway) to NW 12th Street much like a freeway or expressway, though all intersections on Commerce are at-grade.

A major reconstruction on US-77 through Norman completed in April 2009 has realigned US-77 to 12th Avenue East from SH-9 to Tecumseh Road, then west along Tecumseh Road to Flood Avenue, and finally north along Flood Avenue until it merges onto Northbound Interstate-35, the interchange of US-77 and Interstate-35 was modernized and upgraded as part of the widening to six lanes of Interstate-35 to Norman. It formerly ran through downtown Norman along Classen Boulevard, Porter Avenue then west along Robinson Street to Flood Avenue. The north–south section of the new alignment along 12th Avenue was previously flagged as SH-77H.[2]

I-35 and US-77 remain together until the Fort Smith Junction in downtown Oklahoma City, where it transfers onto Interstate 235. At Interstate 44, I-235 ends, but US-77 continues northbound as a freeway, called the Broadway Extension. The Broadway Extension is a major freeway linking the downtown area to Edmond. In Edmond, it heads east to meet I-35, which it joins again until Guthrie, where it splits off.

US-77 has followed Commerce entirely through the Ardmore city limits since 1950 when that thoroughfare was built in its current form as an early bypass along what was then Ardmore's west side to provide a straighter route for through traffic and relieve downtown traffic congestion, replacing the original US-77 route in Ardmore which followed Broadway east from Commerce to "E" Street, north on "E" Street to 12th and west on 12th back to Commerce before proceeding north on Commerce out of the city.

State Highway 77S lies in Love County and Carter County, serving Lake Murray. It has four termini. The main segment of the highway is U-shaped, with its northwestern terminus in Ardmore in Carter County, then heading south to intersect US-70, and running west of Lake Murray. It crosses into Love County, encircling the south shores of the lake before turning north again, re-entering Carter County, with its northeastern terminus at US-70.

Two other segments of SH-77S connect the main loop with other nearby highways. One runs along the Love–Carter county line, connecting to I-35 at exit 24, as well as US-77. The other runs south to SH-32 east of Marietta.